NOP56 Gene - Ribosome Biogenesis and Neurodegeneration
NOP56 encodes a core component of the box C/D small nucleolar ribonucleoprotein (snoRNP) complex, essential for ribosomal RNA 2'-O-methylation and pre-rRNA processing. Mutations cause spinocerebellar ataxia type 36 (SCA36) and are implicated in cancer.
Gene Information Card
| Symbol | NOP56 |
|---|---|
| Full Name | NOP56 ribonucleoprotein |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 10528 ncbi.nlm.nih.gov/gene/10528 |
| Ensembl ID | ENSG00000101361 |
| UniProt ID | O00567 |
| OMIM ID | 614154 |
| HGNC ID | 15911 |
| Aliases | NOL5A, SCA36, NOP56/58, NOP5, NOP5A |
Description
NOP56 (NOP56 ribonucleoprotein) is a protein-coding gene located on chromosome 20p13. It encodes a core component of the box C/D small nucleolar ribonucleoprotein (snoRNP) complex, which catalyzes 2'-O-methylation of ribosomal RNA (rRNA) and is essential for pre-rRNA processing and ribosome biogenesis. The protein interacts with NOP58, fibrillarin, and 15.5K (SNU13) to form the functional snoRNP particle. NOP56 is ubiquitously expressed, with highest levels in the brain, testis, and lymphoid tissues. Pathogenic expansions of an intronic (GGCCTG)n repeat in NOP56 cause spinocerebellar ataxia type 36 (SCA36), a late-onset neurodegenerative disorder. Somatic mutations and altered expression of NOP56 have been reported in various cancers, including colorectal and lung cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia type 36 (SCA36) | Intronic (GGCCTG)n hexanucleotide repeat expansion leads to RNA foci formation, sequestration of RNA-binding proteins, and repeat-associated non-AUG (RAN) translation, resulting in toxic protein products and neuronal degeneration. | OMIM #614153; Kobayashi et al., 2011 (PMID: 21926999) |
| Colorectal cancer | NOP56 overexpression promotes ribosome biogenesis and cell proliferation; knockdown reduces tumor growth in vitro and in vivo. | COSMIC; PMID: 28431213 |
| Lung cancer | NOP56 is upregulated in non-small cell lung cancer (NSCLC) and associated with poor prognosis; silencing NOP56 inhibits cell proliferation and induces apoptosis. | COSMIC; PMID: 30328014 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 15.2 | High |
| Testis | 14.8 | High |
| Lymph node | 12.1 | Medium |
| Liver | 8.5 | Medium |
| Heart | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 (embryonic kidney) | 14.5 | High expression; commonly used for functional studies |
| HeLa (cervical carcinoma) | 13.2 | High expression |
| A549 (lung carcinoma) | 11.8 | Medium-high expression |
| HCT116 (colorectal carcinoma) | 12.4 | High expression |
| K562 (leukemia) | 10.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| (GGCCTG)n expansion (intron 1) | Hexanucleotide repeat expansion | ~0.001% (rare) | Pathogenic; causes SCA36 via RNA toxicity and RAN translation |
| c.1A>G (p.Met1Val) | Missense (start loss) | <0.01% | Likely loss of function; reported in cancer (COSMIC) |
| c.124C>T (p.Arg42Trp) | Missense | <0.01% | Unknown significance; somatic in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., start codon loss, truncating variants) impair snoRNP assembly and rRNA methylation, reducing ribosome biogenesis and cell growth. Rare in germline; observed somatically in cancer.
Gain of Function (GOF)
No confirmed gain-of-function mutations. The (GGCCTG)n expansion in SCA36 is considered a toxic gain-of-function at the RNA level (RNA foci, RAN translation).
Dominant Negative (DN)
Not established for NOP56. The SCA36 expansion is thought to act via a dominant toxic mechanism rather than dominant-negative protein effect.
View complete mutation data：
Gene Ontology (GO)
| • nucleolus (GO:0005730) | • nucleoplasm (GO:0005654) |
| • box C/D snoRNP complex (GO:0031428) | • RNA binding (GO:0003723) |
| • rRNA methyltransferase activity (GO:0008649) | • rRNA processing (GO:0006364) |
| • endonucleolytic cleavage involved in rRNA processing (GO:0000478) | • maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462) |
Pathways
• Ribosome biogenesis in eukaryotes (KEGG: hsa03008)
• rRNA processing in the nucleolus (Reactome: R-HSA-6791226)
• Major pathway of rRNA processing in the nucleolus and cytosol (Reactome: R-HSA-6790901)
Protein Summary
NOP56 is a 594-amino-acid protein (molecular weight ~66 kDa) localized primarily to the nucleolus. It contains a NOP5/NOP56 domain and a coiled-coil region. As a core component of the box C/D snoRNP complex, it binds directly to NOP58 and SNU13, and recruits fibrillarin (FBL) to guide 2'-O-methylation of specific rRNA residues. This modification is critical for proper rRNA folding, ribosome assembly, and translational fidelity. NOP56 also participates in pre-rRNA cleavage at sites A0, A1, and A2. The protein is highly conserved across eukaryotes. Post-translational modifications include phosphorylation and ubiquitination, which regulate its stability and interaction with snoRNAs.
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